The Interleukin-12/Interferon-γ Pathway and Susceptibility to <i>M. Tuberculosis</i> and Nontuberculous Mycobacteria

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  • Kusuhara Koichi
    Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University
  • Takada Hidetoshi
    Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University
  • Hara Toshiro
    Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University

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  • 結核菌／非結核性抗酸菌に対する易感染性とＩＬ‐１２／ＩＦＮ‐γ経路

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Abstract

The Interleukin (IL)-12/Interferon (IFN)-γ pathway plays a pivotal role in immune defense against mycobacteria through killing of intracellular bacteria. Recently, genetic analysis of severe or recurrent cases of clinical diseases caused by weakly virulent mycobacterial species, such as BCG and nontuberculous mycobacteria, have revealed the congenital deficiencies of the molecules involved in the IL-12/IFN-γ pathway designated as ‘Mendelian susceptibility to mycobacterial disease’ (MSMD). Increased susceptibility to tuberculosis has also been observed in this type of genetic disorder. In this paper, we review the clinical manifestations, pathogenesis and genetic analysis of MSMD, with special reference to partial autosomal dominant IFN-γ receptor 1 deficiency, which we first identified in Japanese. We also refer to our gene-based association analysis of 21 candidate genes using marker single nucleotide polymorphisms, in which it is suggested that genetic variants of IL12RB1 confer genetic susceptibility to tuberculosis, and are associated with the progression of the disease in Japanese.

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